Stephanie Fox-Rawlings, National Center for Health Research: July 26, 2018
Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings. Our Center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.
New treatment options for COPD could greatly improve patients’ lives. However, new products must provide a real and clinically meaningful benefit, not just a hope that the treatment works. Unfortunately, the clinical trial data presented today do not provide substantial evidence that mepolizumab [Nucala] provides this benefit for patients with COPD and high eosinophil counts.
One major issue is how to define and distinguish eosinophilic COPD. There is not a consensus in the scientific literature or clinical practice. In part, this may be because a patient’s cell levels fluctuate over time. The sponsors provided one set of thresholds for their clinical trials. However, the clinical trial data do not demonstrate that these are an necessarily appropriate thresholds for clinical practice.
It is important for any indication to be specific enough to accurately select only those patients likely to benefit. This is especially important in this case.
#1: Because the condition is still inadequately defined. As such, it is questionable whether the FDA should approve a drug for such a condition.
#2: The data suggest that patients with low cell counts could have higher rates of moderate to severe exacerbations.
If the clinical trial criteria [for “High Stratum” or eosinophilic] are determined to acceptably describe the patient population who would likely benefit, then there is still the problem that that the clinical trials do not demonstrate that this drug works. While one trial showed a statistically significant decrease in moderate to severe exacerbations, the other trial did not.
In addition, the secondary endpoints do not support efficacy. This raises concerns that the improvement in the successful clinical trial was due to specific conditions of the trial and would not be generalizable. For example, there may be a difference in populations, such as asthma history.
And unfortunately, the effect may not be to be long-lasting based on the limited period of change for the SGRQ score. Patients would be expected to use the drug for years, so if this proved to be the case, it would result in many patients exposed to the risks of adverse events without expectation of benefit.
This drug may increase the risk of adverse events, including heart problems and infections. This risk should be offset by a clinically meaningful improvement in COPD symptoms. It is not clear that this is the case.
This drug may be helpful for a specific subset of patients. But if so, that subgroup of patients needs to be well defined. It is necessary to identify the population that has the potential to benefit, otherwise sick patients will be given the drug and exposed to risk for adverse events without the expectation for benefit. Neither hope nor the placebo effect provide enough benefit to offset risk for adverse events.
The Pulmonary-Allergy Drugs Advisory Committee (PADAC) voted 16 to 3 against approval for mepolizumab as an add-on treatment to inhaled corticosteroid-based maintenance treatment for the reduction of exacerbations in patients with chronic obstructive pulmonary disease (COPD) guided by blood eosinophil counts. Read more about the meeting here.